se6b00396_si_001.pdf (181.76 kB)
pH-Dependent Cellular Internalization of Paramagnetic Nanoparticle
journal contribution
posted on 2016-08-10, 00:00 authored by Branislava Janic, Mohammed
PI. Bhuiyan, James R. Ewing, Meser M. AliA hallmark
of the tumor microenvironment in malignant tumor is
extracellular acidosis, which can be exploited for targeted delivery
of drugs and imaging agents. A pH sensitive paramagnetic nanoaparticle
(NP) is developed by incorporating GdDOTA-4AmP MRI contrast agent
and pHLIP (pH Low Insertion Peptide) into the surface of a G5–PAMAM
dendrimer. pHLIP showed pH-selective insertion and folding into cell
membranes, but only in acidic conditions. We demonstrated that pHLIP-conjugated
Gd44-G5 paramagnetic nanoparticle binds and fuses with
cellular membrane at low pH, but not at normal physiological pH, and
that it promotes cellular uptake. Intracellular trafficking of NPs
showed endosomal/lysosomal path ways.